Understanding how people think, act, and feel ultimately requires understanding how neural circuits interact spatially and temporally. This level of understanding requires fundamentally new tools that are high-throughput, direct, and non-invasive. Current methods are unable to satisfy all of these requirements simultaneously. An ideal tool would provide direct access to tens of thousands of individual neurons while not damaging the surrounding tissue. Electrodes made from metals, silicon, and carbon fibers are relatively hard and brittle making them inherently bio-incompatible. Using electropolymerization, we have produced <500 nm diameter conducting polymer nanowires with a Young's modulus of <1 GPa, two orders of magnitude more elastic than current state-of-the-art carbon fiber electrodes. Recent work has shown that elastic materials, with a Young's modulus similar to that of tissue, are essential for the long term success of implanted devices. We expect that conducting polymer nanowires, better matched to the elasticity of the brain, will provide significantly improved compatibility with neural tissue compared to current electrodes. Our goal is to generate insulated conducting polymer nanowires and attach these nanowires to individual cells for controlled depolarization. Preliminary research has generated conducting polymer nanowires with diameters of <500 nm and lengths ranging from 800 nm to 10 mm. However, cellular measurement and modulation requires an insulated nanowire. Within Aim 1 we will generate nanowires insulated with borosilicate. Aim 2 will functionalize the nanowires with albumin to attach the nanowires to individual cells via albumin receptors on the cell surface. Future research will focus on covalent attachment of application-specific molecules. Aim 3 will use individual nanowires to control the membrane potential of cells. While this R21 is limited to the construction of a prototype device for use on the cellular level, our long-term goal is to work with collaborators to extend this tool to behaving animals. Our initial studies focus on neural modulation. In the future, the same nanowires can be functionalized for measurement as well as modulation. The ability to track neural activity in awake, active, animals at the single cell level requires new tools that are both smaller and higher- throughput, in addition to biocompatible. This research will develop an entirely new nano-scale tool for neural measurement and modulation on a single cell level.